Atherosclerosis is initiated early in human life in an occult manner due to a variety of genetic, environmental and behavioral risk factors and is the leading cause of cardiovascular disease (CVD) events. It originates by the generation of sub-intimal macrophage foam cells that arise mainly due to the accumulation of oxidized lipids through unregulated uptake by macrophage scavenger receptors, an arm of the innate immune response in removing toxic substances to protect the host. After a long latent period of integrative and detrimental insults to the vessel wall, such as oxidation and chronic inflammation, it manifests clinically as either symptomatic obstructive disease such as angina or claudication, or acute atherothrombosis such as myocardial infarction and ischemic stroke.
Various degrees of subclinical atherosclerosis are almost universally present in people living in Western societies. However, the assessment of the specific future risk that subclinical atherosclerosis confers is difficult to assess at the individual level, even with invasive and expensive testing. This is due to the variable nature of its clinical expression, which is in part a consequence of the qualitative differences in plaque components in similar sized lesions. Furthermore, the current clinical paradigm of treating asymptomatic patients is appropriately focused on treating underlying risk factors and is not generally centered on treating only those patients with documented presence of atherosclerosis. In addition, aside from hypolipidemic therapies, specific treatments that target pathogenic mechanisms leading to clinical events, such as the oxidative, immune and inflammatory components, do not yet exist.